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Chemical Development of Therapeutic Oligonucleotides

  • Karin E. LundinEmail author
  • Olof Gissberg
  • C. I. Edvard Smith
  • Rula Zain
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2036)

Abstract

The development of several different chemical modifications of nucleic acids, with improved base-pairing affinity and specificity as well as increased resistance against nucleases, has been described. These new chemistries have allowed the synthesis of different types of therapeutic oligonucleotides. Here we discuss selected chemistries used in antisense oligonucleotide (ASO) applications (e.g., small interfering RNA (siRNA), RNase H activation, translational block, splice-switching, and also as aptamers). Recently approved oligonucleotide-based drugs are also presented briefly.

Key words

Base analogs Ribose modifications Phosphodiester linkage Phosphorodiamidate morpholino (PMO) Locked nucleic acid (LNA) Peptide nucleic acid (PNA) Tricyclo-DNA 

Notes

Acknowledgments

This work was supported by the Swedish Research Council, the Stockholm County Council, Hjärnfonden, and Vinnova/SweLife.

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Authors and Affiliations

  • Karin E. Lundin
    • 1
    Email author
  • Olof Gissberg
    • 1
  • C. I. Edvard Smith
    • 2
  • Rula Zain
    • 1
    • 3
  1. 1.Department of Laboratory Medicine, Center for Advanced TherapiesKarolinska InstitutetStockholmSweden
  2. 2.Department of Laboratory Medicine, Center for Advanced Therapies, Karolinska University Hospital HuddingeKarolinska InstitutetStockholmSweden
  3. 3.Department of Clinical Genetics, Center for Rare DiseasesKarolinska University HospitalStockholmSweden

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